Clinical and biochemical responses to therapy in Alzheimer's disease and multi-infarct dementia

Abstract

Memory performance, central monoaminergic function and sympathetic nerve activity were studied in patients with dementia of the Alzheimer type (DAT) or with multi-infarct dementia before and after 4 weeks with single or combined drug therapy (choline-piracetam). Analysis of the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxyphenylacetic acid (HVA) and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) and also in urine (plus 3-methoxy-4-hydroxy mandelic acid) showed that the basal values of HVA in the CSF and urine were lower in the more severely demented compared with the mildly demented subjects in both groups. The combined drug treatment resulted in a statistically significant increase in the MHPG level in the CSF of mildly demented subjects of the DAT group, while it seemed not to influence the other monoamine metabolites. The sympathetic nerve activity was similar in both patient groups and was unchanged after therapy. These findings suggest a dopaminergic deficit in advanced stages of the disease and a possible enhancement of the central noradrenergic output with therapy. No effects of therapy on memory performance or correlations between monoamine levels and memory test scores were noted.

Cerebrospinal Fluid Markers of Alzheimer's Disease

“…This notion is consistent with the finding that CSF levels of HVA are similar in patients with Parkinson's disease and demented patients with extrapyramidal features 50 . Similarity of CSF HVA in AD patients and patients with multi‐infarct dementia (MID) 41 , 47 , 51 also argues against the specificity of the HVA reduction in AD. Zubenko et al 33 even found an increase of HVA in CSF from patients with only a mild degree of dementia.…”

“…Interpretation of this finding is difficult because it has not been reproduced by other groups as yet. The same holds true for reports on reduction of dopamine‐β‐hydroxylase activity in CSF of AD patients 42–56 …”

“…SLI in CSF does not merely reflect hypothalamic function. Lack of a rostro‐caudal SLI gradient in CSF, as well as the presence of a blood‐CSF barrier for somatostatin, and the good correlation between SLI in brain biopsies and CSF in two AD patients, are all consistent with the notion that changes in CSF SLI reflect alterations in somatostatin secretion of the cerebral cortex 28–59 . All studies on SLI in CSF of AD patients report a reduction of approximately 40% as compared to control populations, which differed among studies 21 , 26 , 28 , 30 , 60–67 .…”

“…MHPG in lumbar CSF, which will be mainly of spinal origin, seems normal in AD 21 , 43–45 , 49 and MID 55 . Only Corona et al 51 found a reduction of 23% in CSF MHPG in AD as compared to MID patients 51 . Interpretation of this finding is difficult because it has not been reproduced by other groups as yet.…”

“…HIAA levels in CSF appear to be of little value in the diagnosis of AD. Reductions ranging from 15% to 40% 38 , 39 , 43–45 , 52 as well as an increase of 85% 53 have been reported, whereas various studies found no differences between AD and control populations 21 , 40 , 41 , 48 , 49 , 51 , 54 . Measurements in CSF of serotonin itself rather than its metabolite HIAA, are variable, depending on the methods used, as shown by Vollicer et al 52 , 54 …”